PB2060: THE MDS-SPECIFIC COMORBIDITY INDEX (MDS-CI) PREDICTS SURVIVAL INDEPENDENTLY FROM DIPSS AND MIPSS70 IN PATIENTS WITH OVERT MYELOFIBROSIS NOT ELIGIBLE FOR ALLOGENEIC STEM CELL TRANSPLANTATION.
Authors: K.-L. Koster, N.-M. Messerich, T. Volken, S. Cogliatti, T. Lehmann, A. Holbro, R. Benz, L. Graf, I. Demmer, W. Jochum, T. Silzle
Journal: HemaSphere (2022)

Background: For several hematological malignancies, both number and severity of comorbidities are prognostically relevant. The MDS-specific comorbidity index (MDS-CI) offers a comprehensive tool to assess the prognostic impact of comorbidities of the major organ systems (see fig A). Its usefulness in patients with overt myelofibrosis (MF) is currently unknown. Aims: To assess the prognostic utility of the MDS-CI in patients with overt MF. Methods: We performed a retrospective chart review of all patients diagnosed with overt MF at our institution between 2000 and 2020 and collected clinical data from hospital records as documented at diagnosis. Patients receiving hematopoietic stem cell transplantation were excluded. For cases lacking next generation Sequencing (NGS) during diagnostic work-up, NGS was performed retrospectively (Oncomine Myeloid Research Assay, Thermo Fisher Scientific, Waltham, MA, USA), if DNA was available from diagnostic samples. Results: 71 patients were evaluable (male n=38, female n=33; age median 73 years, range 28-87; primary MF n=52, MF post ET or PV n=19). During follow-up (median 40 months, range 0-184) 36 patients (51%) died. Median overall survival (OS) was significantly different between the single MDS-CI subgroups: low (n= 38) 100 months (95% CI 65-137), intermediate (n=26) 50 months 95% CI 25-74) and high (n=7) 8 months (95% CI 0-19), p<0.001; see fig. B. The Dynamic International Prognostic Scoring System (DIPSS) was available for all patients (low: n=8, intermediate-1: n=30, intermediate-2: n=25, high: n=8). Since no death occurred in the DIPSS-low-risk group, we split the cohort into a DIPSS lower-risk group (DIPSS low and intermediate-1, n=38) and a DIPSS higher risk group (DIPSS intermediate-2 and high, n= 33) for further analyses. After inclusion of the MDS-CI as a categorical variable (reference group low-risk) into a Cox regression model together with the DIPSSdich, the MDS-CI retained its independent prognostic value (MDS-CI intermediate HR 2.05, 95% CI 1.0-4.15, p= 0.046 and MDS-CI high HR 13.2 (95% CI 4.0-43.1, p<0.001). The Molecular International Prognostic Scoring System 70 (MIPSS70) was available for 57 patients (MIPSS70-low n=2, MIPSS70-intermediate n=42, MIPSS70-high n=13). Within the MIPSS70-intermediate group, the MDS-CI subgroups were associated with significant differences of the median OS: MDS-CI low [n=23]: 115 months [95% CI 76-154], MDS-CI intermediate [n=14]: 89 months [95% CI 50-128] and MDS-CI high [n=5] 11 months [95% CI NA], p=0.007; see fig. C. Despite the low patient numbers, significant differences regarding the median OS were observed for patients within the MIPSS-high risk group as well: MDS-CI low (n=2): median OS 44 months [95% CI NA], MDS-CI intermediate (n=9): median OS 25 months [95% CI 13-37] and MDS-CI high (n=2): median OS 1 months [95% CI NA], p=0.001. Since no death occurred in the MIPSS70-low risk group, we dichotomized the cohort into a MIPSS70-lower group (MIPSS70-low- and -intermediate, n=44) and a MIPSS70high risk group (n=13) for further analysis. The MDS-CI added prognostic information after inclusion into a multivariate model together with the MIPSS70dich (MDS-CI high-risk HR 18.7, 95% CI 4.64-75.6, p<0.001; MDS-CI-intermediate HR 1.66, 95% CI 0.68-1.06, p=0.2674). Image:Summary/Conclusion: The analysis of our small and retrospective cohort suggests that the MDS-CI represents a useful tool in daily clinical practice to assess the prognostic impact of comorbidities in patients with overt MF. However, analyses of larger cohorts are desirable.